Funding agencies: This study was supported by the Deutsche Forschungsgemeinschaft (KFO 114 and FR 1561/4-1) and by the German Federal Ministry of Education and Research in the form of grants to the German Center for Diabetes Research (DZD e.V., 01GI0925) and to the Kompetenznetzwerk Adipositas (01GI0849).
Polymorphism rs3123554 in CNR2 reveals gender-specific effects on body weight and affects loss of body weight and cerebral insulin action
Article first published online: 25 JAN 2014
Copyright © 2013 The Obesity Society
Volume 22, Issue 3, pages 925–931, March 2014
How to Cite
Ketterer, C., Heni, M., Stingl, K., Tschritter, O., Linder, K., Wagner, R., Machicao, F., Häring, H.-U., Preissl, H., Staiger, H. and Fritsche, A. (2014), Polymorphism rs3123554 in CNR2 reveals gender-specific effects on body weight and affects loss of body weight and cerebral insulin action. Obesity, 22: 925–931. doi: 10.1002/oby.20573
Disclosure: The authors have not conflict of interest.
- Issue published online: 5 MAR 2014
- Article first published online: 25 JAN 2014
- Accepted manuscript online: 9 JUL 2013 09:16AM EST
- Manuscript Accepted: 26 JUN 2013
- Manuscript Received: 30 DEC 2012
The cannabinoid-receptor system is involved in the regulation of food intake. Here, we test whether single nucleotide polymorphisms (SNPs) in CNR2, encoding the cannabinoid-receptor 2, are associated with weight in a cross-sectional cohort. Furthermore, we wanted to investigate if the identified hits influence weight loss during lifestyle intervention; and study a potential involvement of cerebral insulin action.
2006 subjects at increased risk for type 2 diabetes mellitus were genotyped for 5 tagging SNPs in the CNR2 locus. All subjects underwent a 75-g OGTT. 345 subjects participated in a lifestyle intervention (TUebingen Lifestyle Intervention Programme). Cerebrocortical insulin sensitivity was measured by magnetoencephalography after intranasal insulin application in 43 subjects.
In the cross-sectional cohort, the minor allele of rs3123554 was associated with lower BMI (Padd = 0.01, Prec = 0.004), and this was attributable to its effect in women only. Interestingly, during lifestyle intervention, carriers of the same allele lost less body weight (Padd = 0.03, Prec = 0.008). Moreover, carriers of this minor allele showed lower cerebral insulin sensitivity (Prec = 0.0402).
The minor allele of rs3123554 is associated cross-sectionally with lower body weight, whereas during intervention the same allele led to less reduction of body weight. Reduced cerebral insulin sensitivity in carriers of this allele might contribute to these disadvantageous effects during lifestyle intervention.